POS1018 ROLE OF THE SIGNALING LYMPHOCYTE ACTIVATION MOLECULE FAMILY IN RHEUMATOID ARTHRITIS COMPLICATED WITH INTERSTITIAL LUNG DISEASE
Authors: Q. Che, J. Chen, Y. Zhang, C. Ren, X. Zhang, W. Hongxing, Q. Shu
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Interstitial lung disease (ILD) is the most common extra-articular complication of rheumatoid arthritis (RA). The prevalence of RA with ILD is approximately 20% and the risk of ILD is significantly higher in RA patients than in healthy controls [1]. The pathogenesis of RA-ILD has not been elucidated, although various genetic, immunological, and environmental factors have been suggested to be involved in its development and progression [2]. Therefore, it is crucial to explore new targets and predictors of RA-ILD pathogenesis. <h3>Objectives</h3> To explore the possible mechanisms involved in the initiation and progression of RA-ILD. <h3>Methods</h3> Synovial samples of RA (GSE55235), lung samples of ILD (GSE53845 and GSE81292) were extracted from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) analysis, weight gene co-expression network analysis (WGCNA) and Consensus Cluster were implemented with R language. Enrichment analysis and shared hub gene analysis were then performed. The function of selected gene signatures and hub genes were validated in external datasets (synovial tissues of RA (GSE55457) and RA-associated usual interstitial pneumonia (RA-UIP) (GSE199152)), in terms of single cells level, RA-ILD patients and our collagen-induced arthritis (CIA) relative ILD animal model. <h3>Results</h3> The ILD relative gene signatures which contained 90 shared genes was obtained (Figure 1 A). KEGG pathway enrichment analysis identified cytokine-cytokine receptor interactions and chemokine signaling pathways (Figure 1 B). CytoHubba selected 17 hub genes as shown Figure 1 C. Validated the 17 hub genes in lung tissue samples from three RA-UIP patients and four non-UIP controls with the external database (Figure 1 D). In single cell port, the surface molecules of B cells, CD19, CD27, CD38, CD79A, SLAMF1, SLAMF2 and SLAMF7 can be detected in RA synovial tissues and lung samples of ILD (Figure 1 E). The SLAMF1, SLAMF2 and SLAMF7 in PBMCs of RA-ILD patients were highly expressed (Figure 1 F). Furthermore, we constructed the CIA+TNF animal model，whose lung pathology showed ILD-like manifestations (Figure 1 G), together with an increased infiltration of B cells, especially those expressing SLAMF1, SLAMF2 and SLAMF7 in both synovial and pulmonary tissues (Figure 1 H). <h3>Conclusion</h3> Our study explored the common pathogenic mechanisms of RA and ILD, identified the shared 17 hub genes of RA-ILD. Especially the SLAMF1, SLAMF2 and SLAMF7 expressing B cells can migrate to pulmonary and take part in the development of fibrosis and ILD, with the guide of chemokines. This indicated a joint-lung axis hypothesis might play important roles in the development and progression of RA-ILD. <h3>References</h3> [1] Spagnolo P, Lee JS, Sverzellati N, Rossi G, Cottin V: The Lung in Rheumatoid Arthritis: Focus on Interstitial Lung Disease. Arthritis Rheumatol 2018, 70(10):1544-1554.https://doi.org/10.1002/art.40574 [2] Kadura S, Raghu G: Rheumatoid arthritis-interstitial lung disease: manifestations and current concepts in pathogenesis and management. Eur Respir Rev 2021, 30(160).https://doi.org/10.1183/16000617.0011-2021 <h3>Acknowledgements</h3> Funded by the ECCM Program of Clinical Research Center of Shandong University (No. 2021SDUCRCB010), the Natural Science Foundation of Shandong Province (ZR2021QH329) and the Natural Science Foundation of Shandong Province (ZR2022MH177). <h3>Disclosure of Interests</h3> None Declared.